Lab of Molecular Imaging and Translational Medicine (MITM), Engineering Research Center of Molecular and Neuro Imaging, Ministry of Education, School of Life Science and Technology, Xidian University, Xi'an, Shaanxi 710126, P.R. China.
Department of Thoracic Surgery, Shanghai Pulmonary Hospital, School of Medicine, Tongji University, Shanghai 200433, China.
Nano Lett. 2022 Oct 26;22(20):8250-8257. doi: 10.1021/acs.nanolett.2c02983. Epub 2022 Oct 11.
Photodynamic therapy (PDT) holds great promise in tumor therapy due to high safety, efficacy, and specificity. However, the risk of increased metastasis in hypoxic tumors after oxygen-dependent PDT remains underestimated. Here, we propose a post-PDT oxygen supply (POS) strategy to reduce the risk of metastasis. Herein, biocompatible and tumor-targeting Ce6@BSA and PFC@BSA nanoparticles were constructed for PDT and POS in a 4T1-orthotropic breast cancer model. PDT with Ce6@BSA nanoparticles increased tumor metastasis via the HIF-1α signaling pathway, whereas POS significantly reduced the PDT-triggered metastasis by blocking this pathway. Furthermore, POS, with clinical protocols and an FDA-approved photosensitizer (hypericin), and oxygen inhalation reduced PDT-induced metastasis. Our study findings indicate that PDT may increase the risk of tumor metastasis and that POS may solve this problem. POS can reduce the metastasis resulting not only from PDT but also from other oxygen-dependent treatments such as radiotherapy and sonodynamic therapy.
光动力疗法（PDT）由于其高安全性、有效性和特异性，在肿瘤治疗中具有很大的应用前景。然而，在缺氧肿瘤中进行氧依赖性 PDT 后转移风险增加的风险仍被低估。在这里，我们提出了一种 PDT 后氧供应（POS）策略，以降低转移的风险。在此，构建了具有生物相容性和肿瘤靶向性的 Ce6@BSA 和 PFC@BSA 纳米粒子，用于 4T1 原位乳腺癌模型中的 PDT 和 POS。Ce6@BSA 纳米粒子的 PDT 通过 HIF-1α 信号通路增加了肿瘤转移，而 POS 通过阻断该通路显著降低了 PDT 引发的转移。此外，POS 与临床方案和 FDA 批准的光敏剂（hypericin）和吸氧一起减少了 PDT 诱导的转移。我们的研究结果表明，PDT 可能会增加肿瘤转移的风险，而 POS 可能会解决这个问题。POS 不仅可以减少 PDT 引起的转移，还可以减少放疗和声动力治疗等其他依赖氧的治疗引起的转移。
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